OVERALL DESCRIPTION (Adapted from application): This Program Project Application is submitted by an interactive group of basic and clinical scientists who propose to continue to study the mucosal immune system inr elation to parasitic, bacterial and viral infections. The proposed research focuses on the broad areas of pathogenesis, prevention and therapy of important diseases caused by different classes of infectious agents that infect the gastrointestinal, genital and respiratory mucosae. Project 1 addresses Entamoeba histolytica and amoebiasis, a leading cause of parasitic death and morbidity worldwide. The specific studies focus on the galactose-inhabitable lectin, that mediates the binding of Entamoeba to the intestinal epithelium. The goal is to identify immunogenic subdomains of the lectin that can be used to develop an effective oral subunit vaccine. The second project is on Helicobacter pylori, the major cause of peptic ulcer disease. Based upon studies of pathogenesis and mechanisms of immune defense, a major goal is to develop prophylactic and therapeutic vaccines that do not elicit an untoward inflammatory immune defense, a major goal is to develop prophylactic and therapeutic vaccines that do not elicit an untoward inflammatory immune response. Project 3 investigates how mucosal IgA antibodies can counter HIV at epithelial surfaces that are the portals of entry for sexual transmission of this virus. Monoclonal IgA antibodies to HIV, both extracellular and intracellularly. The mechanisms of action of such protection will be studied. The results may further the design of an effective mucosal vaccine for this sexually transmitted disease. The fourth project investigates IgA nephropathy, the most common type of glomerulonephritis, that is associated clinically with respiratory infection The roles that normal and aberrant IgA glycosylation, virus-specific T cells and glomerular mesangial cells play in disease pathogenesis will be investigated in a post infection mouse model in nephritis-sensitive and nephritis-resistant strains. The four projects are supported by administrative and hybridoma cores. The insights to be gained from this PROGRAM Project may e broadly applicable since many infections involve mucous membranes, either as sites of infection or as portals of entry into the host.